The potential anti-inflammatory effect of tetrahydrobiopterin administration in renal mass reduction-induced chronic renal failure in rats

Saudi Med J. 2007 Dec;28(12):1803-9.

Abstract

Objective: To investigate the impact of tetrahydrobiopterin (BH4) supplementation on the markers of inflammation, and on the histological picture of the kidney in chronic renal failure C-reactive protein (CRF) induced in rats by subtotal nephrectomy (SNx).

Methods: This study was performed at the Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia during the period from December 2005 to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister rats, and another 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received 10mg kg-1 BH4 intraperitoneally daily for 4 weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde (MDA), and kidney functions were measured in all rats. Histopathological examination of the kidney tissues was also performed.

Results: Untreated CRF rats showed significant elevation of plasma CRP, IL-6, and MDA levels, and significant decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis and, interstitial tubular infiltration with inflammatory cells in comparison with the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, and MDA levels, and decreased tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats.

Conclusion: Supplementation with exogenous BH4 decreased markers of inflammation and protected the kidney against post-renal mass reduction histologic damage. Restoration of intracellular BH4 balance could normalize nitrous oxide production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality of this disease.

MeSH terms

  • Animals
  • Biopterins / analogs & derivatives*
  • Biopterins / pharmacology
  • C-Reactive Protein / metabolism*
  • Disease Models, Animal
  • Interleukin-6 / blood*
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / pathology*
  • Kidney Function Tests
  • Male
  • Malondialdehyde / blood
  • Nephrectomy
  • Rats
  • Rats, Wistar

Substances

  • Interleukin-6
  • Biopterins
  • Malondialdehyde
  • C-Reactive Protein
  • sapropterin